Long non-coding mitochondrial RNAs as potential targets for diagnosis and therapy of bladder cancer

Bladder cancer (BC) is a heterogeneous disease with 70% of patients presenting superficial tumours and 30% presenting muscle-invading disease with a high risk of death associated to metastasis. The diagnosis is carried out by urine cytology, whith high specificity but low sensitivity, and cystoscopy, an expensive and unpleasant procedure. Carcinoma in situ and other high grade non-muscle-invasive tumors are treated by intravesical administration of BCG or other chemotherapeutic agents, while the indication for muscle-invasive disease is radical cystectomy. Human cells express a family of mitochondrial long non-coding RNAs (ncRNAs). One of these transcripts, the sense mitochondrial ncRNA or SncmtRNA, is expressed in normal proliferating cells and tumor cells but not in non-dividing cells. In addition, normal human proliferating cells express two antisense transcripts, ASncmtRNA-1 and ASncmtRNA-2. Strikingly however, the ASncmtRNAs are down-regulated in tumor cell lines as well as in tumor cells present in different types of human cancer, including BC. Therefore, the differential expression profile of these transcripts allows to detect cancer cells in biopsies and biological fluids. Down-regulation of the ASncmtRNAs seems to be an important hallmark of cancer and, hypothetically, may also represent a general vulnerability of cancer cells. Indeed, knock-down of the ASncmtRNAs using antisense oligonucleotides (ASO) exerts negative effects on cell proliferation and viability of bladder cancer cell lines representing a novel therapeutic strategy for this disease. We discuss recent advances on the use of the mitochondrial ncRNAs as targets for diagnostic and therapeutic protocols of BC and its potential use in the clinic.